ライフサイエンスコーパス: IL-2

1 IL-2 alone (0.3 x 10(6) IU/m(2) or 1 x 10(6) IU/m(2)) or

2 IL-2 drives terminal differentiation, generating cells t

3 IL-2 has been shown to have therapeutic efficacy for imm

4 IL-2 has emerged as a critical immunomodulatory cytokine

5 IL-2 is a critical regulator of immune homeostasis throu

6 IL-2 is a pleiotropic cytokine and a key survival factor

7 IL-2 is a pleotropic cytokine with potent pro- and anti-

8 IL-2 promoted effector-like metabolism and aerobic glyco

9 IL-2 signals are propagated, in part, via activation of

10 IL-2/alphaIL-2 complexes highly efficiently expanded per

11 FN-gamma (P < 0.001), TNF-alpha (P = 0.004), IL-2 (P = 0.004) and IL-4 (P = 0.009) median levels were

12 ant protein 1 (P = .028), RANTES (P = .005), IL-2 (P = .002), and IL-17 (P = .007) during viral URIs

13 ncentrations of antigen-specific T-helper 1 (IL-2, IL-12, interferon-gamma) and T-helper 2 (IL-4, IL-

14 n of inflammatory mediators including IL-17, IL-2, TNF, and IFN-gamma.

15 s (TNFa, IL-1beta, IL-22, IL-33, IL-17alpha, IL-2, MIP-2, and MCP-1), and neutrophil infiltration (my

16 ased total production of IFNgamma, IL-1beta, IL-2, and TNFbeta.

17 ve of the parental MSCs, including IL-1beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12(p40), I

18 ase studies reporting on levels of IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, CRP, TNF-alp

19 ted for pro-inflammatory cytokines IL-1beta, IL-2, IL-6, IL-8 and TNF-alpha, prior to starting with t

20 -gamma or genetic deletion of interleukin 2 (IL-2) receptor common gamma chain in Rag-deficient mice

21 Interleukin 2 (IL-2) was an important upstream regulator of CD4+ T cell

22 kines in the serum, including interleukin 2 (IL-2), IL-6, IL-12 (p70), tumor necrosis factor (TNF), a

23 but not PD1, TIM-3, CTLA4, or interleukin 2 (IL-2).

24 Interleukin-2 (IL-2) and IL-15 play pivotal roles in T cell activation,

25 The pleiotropic actions of interleukin-2 (IL-2) are essential for regulation of immune responses a

26 of low-dose recombinant human interleukin-2 (IL-2) combined with low-dose rapamycin to prolong graft

27 Injection of Interleukin-2 (IL-2) complexed with a particular anti-IL-2 monoclonal a

28 action; and, second, relative interleukin-2 (IL-2) deprivation.

29 Interleukin-2 (IL-2) has both pro- and anti-inflammatory properties tha

30 Interleukin-2 (IL-2) is a component of most protocols of adoptive cell

31 Interleukin-2 (IL-2) is a small alpha-helical cytokine that regulates i

32 High dose interleukin-2 (IL-2) is active against metastatic melanoma and renal ce

33 +), and this was prevented by interleukin-2 (IL-2) neutralization.

34 and dose-dependently suppress interleukin-2 (IL-2) production and T cell proliferation.

35 ated T cell proliferation and interleukin-2 (IL-2) production.

36 Low-dose interleukin-2 (IL-2) represents a new therapeutic approach to regulate

37 y reduced CD25 expression and interleukin-2 (IL-2) responsiveness, diminished CTLA-4 expression and i

38 ) failed to engraft even with interleukin-2 (IL-2) support.

39 factor alpha (TNF-alpha), and interleukin-2 (IL-2) than control cows, whereas only clinical cows had

40 f the central immune cytokine interleukin-2 (IL-2) that bind to the IL-2 receptor betagamma(c) hetero

41 ty of T cells to the cytokine interleukin-2 (IL-2) through a positive feed-forward loop involving inc

42 to 18.0-fold; P < 0.001) for interleukin-2 (IL-2), and 1.7-fold (CI, 0.1- to 4.0-fold; P = 0.004) fo

43 motif chemokine 10 (CXCL10), interleukin-2 (IL-2), IL-1alpha, transforming growth factor-alpha (TGF-

44 f CD4(+) T cells that express interleukin-2 (IL-2), IL-4, and tumor necrosis factor alpha (TNF-alpha)

45 omponent of the receptors for interleukin-2 (IL-2), IL-4, IL-7, IL-9, IL-15, and IL-21.

46 rying HLA-B -21M or 21T using interleukin-2 (IL-2)-activated NK cells and leukemic cells from patient

47 12, interferon (IFN)-gamma, IFN-alpha, IL-2, IL-2 R, IL-8, macrophage inflammatory protein (MIP)-1alp

48 nctional Ag.pTfh cells with an altered IL-21/IL-2 axis contribute to inadequate vaccine responses.

49 e, we show that, through a functional IL-2R, IL-2 initiates signaling pathways and impacts vascular s

50 lls had preserved early steps of activation, IL-2 production, proliferation, and Th cell polarization

51 Because of these advances, IL-2 is now being tested as a cytokine for suppressing p

52 2Ac in human T effector cells did not affect IL-2-dependent pSTAT5 activation.

53 nded to 10(3) vRNA copies/ml by day 10 after IL-2-DT administration.

54 /-) ILC2 is also restored to WT levels after IL-2 complex treatment, indicating a tissue-specific rol

55 e and cytolytic function were restored after IL-2 stimulation.

56 ess toward donor alloantigens in vitro after IL-2 cplx treatment was stopped.

57 t understanding of the mechanisms that allow IL-2-STAT5 signaling to exert divergent effects across C

58 6, IL-12, interferon (IFN)-gamma, IFN-alpha, IL-2, IL-2 R, IL-8, macrophage inflammatory protein (MIP

59 e expression of CD154, IFN-gamma, TNF-alpha, IL-2, and IL-17 and proliferation.

60 gamma, proinflammatory cytokines (TNF-alpha, IL-2, IL-12p70), and chemokines (CXCL10, C-C motif chemo

61 The release of IFN-gamma, TNF-alpha, IL-2, IL-4, IL-6, IL-10 and IL-17A from isolated, stimul

62 ting cells, as well as IFN-gamma, TNF-alpha, IL-2, IL-6, IL-17A, and KC production by spleen cells.

63 have developed a new IL-2-based biologic, an IL-2/CD25 fusion protein, with greatly improved pharmaco

64 actions on radio-resistant host cells in an IL-2- and IL-15-dependent manner.

65 NK cell responses to activation by IL-15 and IL-2.

66 d DUSP4 expression and imbalanced IL-17A and IL-2 production.

67 ect correlated with a reduction of IL-1A and IL-2, as well as Akt/mTOR phosphorylation.

68 iver, increased serum interleukin (IL)-6 and IL-2, but peripheral regulatory T cell (Treg) numbers di

69 n inhibits 4-1BB-induced cRel activation and IL-2 production to facilitate optimal CD8 T cell immunit

70 e cells express high levels of TNF-alpha and IL-2, and provide B cell help for IgG production in an I

71 human CD4(+) T cells, both TNF-alpha(+) and IL-2(+) vesicles can tether with endocytic organelles (l

72 ti-BCR, CpG oligodeoxynucleotide, CD40L, and IL-2, we were able to obtain more than 90% GZMB(+) B cel

73 ations caused reduced surface expression and IL-2 binding.

74 sion was strictly required for IFN-gamma and IL-2 expression and secretion after T cell activation bu

75 g promoted the accumulation of IFN-gamma and IL-2-producing T cells in skin draining lymph nodes in a

76 ty, and produced the cytokines IFN-gamma and IL-2.

77 ammatory cytokines TNF-alpha, IFN-gamma, and IL-2 more than the anti-inflammatory cytokines IL-4 and

78 ) T cells can be divided into IFN-gamma- and IL-2-producing cells.

79 iosynthesis via the lipoxygenase pathway and IL-2 biosynthesis (all P < .01).

80 st-stimulated secretion of IFNgamma, TNF and IL-2 proteins.

81 -inflammatory genes (IFNgamma, TNFalpha, and IL-2), while CSF1-R and IL17RA were upregulated.

82 While the impacts of systemic IL-2: anti-IL-2 antibody complex (IL-2C) administration are well-de

83 A combination of daclizumab and anti-IL-2 efficiently blocked IL-2-induced proliferation of I

84 n vivo by forming complexes of IL-2 and anti-IL-2 mAbs (IL-2C) to target IL-2 to distinct subsets of

85 eral regulatory T cell (T(reg))-biasing anti-IL-2 antibodies have been developed for combination ther

86 combinant IL-2 with different clones of anti-IL-2 monoclonal antibodies that differentially target th

87 in-2 (IL-2) complexed with a particular anti-IL-2 monoclonal antibody (mab) JES6-1 has been shown to

88 with recombinant IL-2 complexed to the anti-IL-2 mAb JES6-1 in the presence or absence of mugwort po

89 -1beta, IL-5, IL-6 and IL-17 and antitumoral IL-2 and IL-12 in tumor-proximal lymph nodes, and increa

90 d concentrations of T cell cytokines such as IL-2, IL-4, and IL-13, which are produced by these cells

91 ciency in protein O-GlcNAcylation attenuates IL-2/STAT5 signaling, while overexpression of a constitu

92 engineered to sustainably release TGF-beta1, IL-2, and rapamycin, to induce Treg differentiation from

93 daclizumab and anti-IL-2 efficiently blocked IL-2-induced proliferation of IL-2-dependent wild-type (

94 induced CD4(+) T cell responses dominated by IL-2 and TNF production together with CD154 upregulation

95 cifically impairs TCR signal transduction by IL-2-inducible T cell kinase (ITK) due to a requirement

96 findings underscore the role of Treg cells, IL-2, and Blimp-1 in controlling the differentiation of

97 Importantly, by combining IL-2 with donor-specific Tregs, but not with polyclonal

98 oduce abundant p:MHCII complexes and consume IL-2, whereas XCR1(+) DCs weakly produce p:MHCII but do

99 Cs weakly produce p:MHCII but do not consume IL-2.

100 ncreased up to 80% in experiments containing IL-2-DT and only 30% in anti-CCR4-treated RMs, parallele

101 itive (CD4SP) thymocytes and that continuous IL-2 production sustained thymic T reg cell generation a

102 Conversely, IL-2 complex-induced Treg expansion in wild-type mice wi

103 The cytokine IL-2 was discovered as a growth factor for T cells and t

104 os1/2 deficiency, production of the cytokine IL-2 was impaired, differentiation into regulatory T cel

105 AT for an optimal production of the cytokine IL-2.

106 and the surface presentation of a cytokine (IL-2) on ICEp were shown to substantially impact human p

107 k the ability to produce effector cytokines (IL-2, IFN-gamma, IL-17), regardless of differentiation s

108 there was an up-regulation of Th1 cytokines (IL-2 and IFN-gamma) as compared to Th2 cytokines (IL-4 a

109 Denileukin diftitox (DAB-IL-2, Ontak) is a diphtheria-toxin-based fusion protein

110 d that, while both s-DAB-IL-2(V6A) and s-DAB-IL-2 are inhibitors of tumor growth, the capacity to tre

111 for 10 days, both s-DAB-IL-2(V6A) and s-DAB-IL-2 given before checkpoint inhibition with anti-progra

112 hallenge and observed that, while both s-DAB-IL-2(V6A) and s-DAB-IL-2 are inhibitors of tumor growth,

113 that have progressed for 10 days, both s-DAB-IL-2(V6A) and s-DAB-IL-2 given before checkpoint inhibit

114 capacity to treat with higher doses of s-DAB-IL-2(V6A) could provide a superior activity window.

115 s-DAB-IL-2(V6A), a fully monomeric protein with reduced vascul

116 ly active, second-generation biologic, s-DAB-IL-2(V6A), which elicits 50-fold less human umbilical ve

117 lethal to mice by LD(50) analysis than s-DAB-IL-2.

118 D28 antibodies, as demonstrated by decreased IL-2 secretion and proliferation.

119 f T cells with CTLA-4(+) CLL cells decreased IL-2 production.

120 s-of-function studies show that ILC3-derived IL-2 is essential for maintaining T(reg) cells, immunolo

121 cent studies focusing on the use of low-dose IL-2 in transplantation, autoimmunity, and other inflamm

122 for selective response of Tregs to low-dose IL-2 is not fully understood.

123 on with the aim to optimize current low-dose IL-2 regimens.

124 Low-dose IL-2 therapy has been used in several clinical trials to

125 paper, we summarize our findings on low-dose IL-2 treatment in corneal allografting and review recent

126 tization in mice, TGFbeta1-mim downregulated IL-2, IL-4, IL-5, IL-13, and IFN-gamma, upregulated IL-1

127 n -21M patients than in -21T patients during IL-2-based immunotherapy.

128 L-2Rbeta surface expression and dysregulated IL-2/15 signaling, with an anticipated reduction in regu

129 empegaldesleukin (NKTR-214) is an engineered IL-2 cytokine prodrug that provides sustained activation

130 NKTR-214 is a kinetically-engineered IL-2 receptor betagamma (IL-2Rbetagamma)-biased agonist

131 Enhanced IL-2 signaling increased the expression of Foxp3 in thym

132 urvival, and memory in part through enhanced IL-2/IL-2R signaling.

133 ction, and this can be overcome by exogenous IL-2 administration.

134 Although lower concentrations of exogenous IL-2 promoted IL-10(+) cells coproducing proinflammatory

135 e find that IL-2C targeting cells expressing IL-2 receptor beta cause an acute decrease in cellularit

136 son to wildtype replicon, mutants expressing IL-2 injected into murine B16F10 melanoma showed 5.5-fol

137 ls, they express the autocrine growth factor IL-2 which transforms them into rapidly dividing effecto

138 l pool size is scaled by a key niche factor, IL-2, produced by self-reactive CD4SP thymocytes.

139 Finally, IL-2/alphaIL-2 complex-expanded Treg cells could be reca

140 -fold (CI, 2.0- to 15.0-fold; P < 0.001) for IL-2, with no difference for TNF-alpha or CD107a.

141 rt, comprises the high affinity receptor for IL-2, a cytokine important in immune proliferation, acti

142 This reduced the input thresholds for IL-2 secretion in a sensitizer-like fashion.

143 In the Golgi fraction isolated from IL-2-producing ATL cells, we detected by Western blot ph

144 r example, in T cells, some cytokines (e.g., IL-2) are polarized to the T cell-target cell interface,

145 3-expressing T cells produce more IFN-gamma, IL-2, and CD69 compared with T cells that express CXCR3

146 xpansion and cytokine production (IFN-gamma, IL-2, and TNF), with the highest median magnitude detect

147 els of TNF-alpha in REC group and INF-gamma, IL-2, TGF-beta and TNF-alpha in the C-PRO group were als

148 on in vitro in response to interferon-gamma, IL-2 and IL-4 that is reverted by the JAK1/JAK2 inhibito

149 This next-generation IL-2 can also overcome targeted therapy-associated resis

150 Therefore, this next-generation IL-2 reduces toxicity while increasing TILs that potenti

151 ower in transplant GNB vs nontransplant GNB: IL-2 (median [IQR]: 7.1 pg/ml [7.1, 7.1] vs 32.6 pg/ml [

152 ation, sustained cRel activation, heightened IL-2 production and T cell expansion.

153 Hence, IL-2 is not just a growth factor; it lays the foundation

154 However, high IL-2 levels also induced the development of GVHD.

155 oproducing proinflammatory cytokines, higher IL-2 doses, both alone and in combination with dexametha

156 l TCR signal strength correlates with higher IL-2 secretion at early time points following TCR stimul

157 k basal TCR signaling correlated with higher IL-2 secretion at later time points.

158 ocytes, relatively little is known about how IL-2 affects the function of nonlymphoid cells.

159 experimental models and for considering how IL-2 may contribute to the etiology or severity of gut-a

160 Administration of human IL-2 to NSG -( K(b) D(b)) (null) ( IA(null)) mice via ad

161 (alphaCD3), cyclophosphamide (CyP), and IAC (IL-2/JES6-1) antibody complex.

162 controls the Tfh program by influencing IL6/IL-2 production, controlling CD26 extracellular expressi

163 ong-acting mIL-2/CD25 represents an improved IL-2 analog that persistently elevates Tregs to maintain

164 lvement of CD25 suggested a role of BT-11 in IL-2 signaling.

165 specific CD8(+) T cell responses occurred in IL-2-DT-treated RMs.

166 d thiol levels were higher in IL-15- than in IL-2-primed NK cells.

167 ls transfected with IL-2, suggesting that in IL-2-producing cells signaling may already take place be

168 added microenvironmental factors, including IL-2, TGFbeta, and PGE2, direct the conversion from naiv

169 gh modulating cellular iron levels increased IL-2 production by activated T lymphocytes, CD25 express

170 ith zidovudine was associated with increased IL-2 expression after tetanus toxoid stimulation.

171 n tumor-proximal lymph nodes, and increasing IL-2 in the serum of tumor-bearing mice.

172 IL-18, and MIG, as well as anti-inflammatory IL-2 that were upregulated in a correlated fashion.

173 (+)) T cells were evaluated by intracellular IL-2, IFN-gamma, and TNF-alpha production with IL-21 in

174 oma showed 5.5-fold increase in intratumoral IL-2 and 2.1-fold increase in infiltrating CD8 T cells,

175 sal TCR signaling, consistently produce less IL-2, and express PD-1 and markers associated with anerg

176 accompanied by an increase of IL-17 in a low IL-2 setting, which is, nevertheless, likely to be prote

177 Binding to either an anti-mouse IL-2 monoclonal antibody (mAb) or a small molecule inhib

178 In this study, we show that low-dose mouse IL-2/CD25 (mIL-2/CD25), but not an equivalent amount of

179 illiseconds-timescale dynamics of free mouse IL-2 (mIL-2), we identify a global transition to a spars

180 r-targeting antibody (Ab) and a super mutant IL-2 (sumIL-2) with decreased CD25 binding and increased

181 ows superior anti-tumor activity over native IL-2 and systemically expands anti-tumor CD8(+) T cells

182 We have developed a new IL-2-based biologic, an IL-2/CD25 fusion protein, with g

183 f CMV: (i) the nonprotective signature (NPS; IL-2(-)IFN-gamma(+)TNF-alpha(-)MIP-1beta(+)), found at i

184 s also been shown to increase the t (1/2) of IL-2 and further enhance Treg frequencies and function.

185 ) mice are restored by the administration of IL-2 complexes, also leading to improved intestinal tiss

186 donor specificity and the administration of IL-2 to promote in vivo expansion of Treg.

187 mIL-2/CD25), but not an equivalent amount of IL-2, prevents the onset of diabetes in NOD mice and con

188 y fitness, indicating a novel application of IL-2 to boost pathogen-specific T cell memory while simu

189 Fully understanding the biology of IL-2 may enable us to custom-design this cytokine for di

190 ctional, nor does it enhance the capacity of IL-2-based immunotherapeutic strategies to increase thei

191 The combination of IL-2 and rapamycin has the potential to inhibit human is

192 The combination of IL-2 with its mAb (JES6-1) has also been shown to increa

193 be directed in vivo by forming complexes of IL-2 and anti-IL-2 mAbs (IL-2C) to target IL-2 to distin

194 ultures of Tregs with high concentrations of IL-2 or delivery of IL-2 directly to patients could impr

195 Interestingly, when high concentrations of IL-2 were used for in vitro Treg expansion cultures, AA

196 IL-2Rbetagamma)-biased agonist consisting of IL-2 conjugated to multiple releasable polyethylene glyc

197 and, more recently, excessive consumption of IL-2, which are proposed as competing hypotheses.

198 However, the relative contributions of IL-2 and T cell receptor signaling to this process are u

199 Notably, lineage-specific deletion of IL-2 in T cells did not reduce T(reg) cells in the small

200 h high concentrations of IL-2 or delivery of IL-2 directly to patients could improve clinical outcome

201 Here, we show that combining low doses of IL-2 cplxs with rapamycin and blockade of the inflammato

202 eg)) cells(4-8), and the use of low doses of IL-2 has emerged as a potential therapeutic strategy for

203 The protective effects of IL-2 involve the generation, maintenance and function of

204 We observed increased expression of IL-2-associated signaling molecules CD25, STAT5 phosphor

205 ed with higher IgG levels and frequencies of IL-2- and TNF-alpha-producing CD4(+) T cells.

206 and humans showed that the major function of IL-2 is to maintain functional regulatory T cells, and t

207 okine to cells expressing different kinds of IL-2 receptors.

208 se immunized mice produced similar levels of IL-2 and IFN-gamma upon ex vivo stimulation with Ags pre

209 factor-alpha, and IL-10 and lower levels of IL-2 were observed in CDC patients versus controls.

210 n mice, the bioavailability and half-life of IL-2 in vivo can be increased by complexing recombinant

211 Here, we report that the majority of IL-2-producing cells in the thymus are mature CD4 single

212 eliable surface and transcription markers of IL-2/alphaIL-2 complex-expanded Treg along with their ex

213 this study, we report that neutralization of IL-2 in mice abrogated all IL-2R signaling in Treg cells

214 The conformational plasticity of IL-2 plays an important role in its biological actions b

215 c CD4+ T cells, harboring higher portions of IL-2-secreting, but lower portions of IFN-gamma-secretin

216 es demonstrated the therapeutic potential of IL-2 for improving antiparasitic immunity.

217 estingly, TCR stimulation in the presence of IL-2 upregulates intracellular expression of the beta-ga

218 n marker of Treg expanded in the presence of IL-2/alphaIL-2 complexes and allergen.

219 ta-dependent axis promotes the production of IL-2 by ILC3s to orchestrate immune regulation in the in

220 Furthermore, production of IL-2 by ILC3s was significantly reduced in the small int

221 with a profound defect in the production of IL-2, along with increased chromatin accessibility of AP

222 iently blocked IL-2-induced proliferation of IL-2-dependent wild-type (WT) ATL cells but not cells tr

223 ut substantial correction after reduction of IL-2 consumption by hyperactivated CD8(+) T cells.

224 However, the precise role of IL-2 in the maintenance and function of Treg cells in th

225 (ILC3s) are the dominant cellular source of IL-2, which is induced selectively by IL-1beta.

226 -1 receptor (PD-1(+)) subset that depends on IL-2 provided by conventional T cells for optimal homeos

227 ith cognate Ag plus agonist anti-OX40 mAb or IL-2 in vivo.

228 However, T cell proliferation or IL-2 secretion were only triggered by USSN when costimul

229 the extent to which Gal-3 regulates the OX40/IL-2 signaling axis and CD8(+) T cell proliferation, eff

230 ession, which facilitated their preferential IL-2-dependent expansion.

231 Circulating CD4+ T cells produced IL-2 and IFN-gamma after HCV antigen stimulation, demons

232 ver, CXCR3(+) T(N) cells frequently produced IL-2 and TNF in response to nonspecific activation direc

233 that CD4(+) T cells concomitantly producing IL-2 and TNF dominated the responses from vaccinees afte

234 g NC; and (ii) the protective signature (PS; IL-2(+)IFN-gamma(+)TNF-alpha(+)MIP-1beta(+)) found at lo

235 Five RMs received IL-2-DT on ART, but treatment was discontinued because o

236 In this study, we construct a recombinant IL-2 immunocytokine comprising a tumor-targeting antibod

237 o can be increased by complexing recombinant IL-2 with different clones of anti-IL-2 monoclonal antib

238 y mice were treated in vivo with recombinant IL-2 complexed to the anti-IL-2 mAb JES6-1 in the presen

239 rmacodynamics when compared with recombinant IL-2 to enhance this type of immunotherapy.

240 ctivity in mouse Tregs significantly reduced IL-2-dependent STAT5 activation.

241 By contrast, despite substantially reduced IL-2 sensitivity, Treg cells maintained selective IL-2 s

242 ycle anaplerosis are associated with reduced IL-2 production, demonstrating the functional importance

243 LDH inhibition rewired IL-2-induced effects, promoting pyruvate entry into the

244 nhanced presence in lymphoid tissues, robust IL-2 production, and recall potential, greater than expe

245 To address this, we created 2 NOD- scid IL-2 receptor subunit gamma ( IL2rg) (null) (NSG) strain

246 To examine these mechanisms, NOD/SCID IL-2 RG(-/-) humanized mice were either directly infecte

247 sensitivity, Treg cells maintained selective IL-2 signaling and prevented immune dysregulation follow

248 uppressive function, and upregulated several IL-2-regulated genes.

249 While the impacts of systemic IL-2: anti-IL-2 antibody complex (IL-2C) administration

250 of IL-2 and anti-IL-2 mAbs (IL-2C) to target IL-2 to distinct subsets of cells based on their express

251 We demonstrate that IL-2 activates binding of AP-1 and STAT5 at sites that c

252 Finally, we demonstrate that IL-2 expression increases upon initiation of conditions

253 Here we show, in a mouse model, that IL-2 is acutely required to maintain T(reg) cells and im

254 us report from our laboratory, we noted that IL-2 and IL-2Rbeta-deficient mice lose smooth muscle cel

255 lysis of CD4 thymocyte subsets revealed that IL-2 was expressed in self-reactive CD4SP thymocytes, wh

256 producing fixed CD8(+) T cells revealed that IL-2(+) cells produce helper cytokines, and that IFN-gam

257 n for putative IL-10 elicitors revealed that IL-2, IL-4, IL-27, IL-10, and neuromedin U (NMU) increas

258 Here, we show that IL-2 signaling is required to maintain open chromatin at

259 finding, combined with our work showing that IL-2 surrounds vascular smooth muscle cells by associati

260 We have shown that IL-2 augmentation can overcome these mechanisms.

261 The IL-2 receptor (IL-2R) is composed of IL-2Ralpha, IL-2Rbe

262 e, SRC family tyrosine kinase (LCK), and the IL-2-inducible T cell kinase (ITK) with the T cell-speci

263 BT-11 effectively enhances the IL-2/STAT5 signaling axis to induce the differentiation

264 How the IL-2 receptor beta-chain specifically shapes immunity ha

265 ne, independently of gp41, and inhibited the IL-2, IL-4, and IL-7 responses, as well as TCR-mediated

266 of mast cells to allergens and microbes, the IL-2 signaling pathway, and host interactions with virus

267 ug that provides sustained activation of the IL-2 pathway with a bias to the IL-2 receptor CD122 (IL-

268 d loop involving increased expression of the IL-2 receptor alpha-subunit and activation of the transc

269 on gamma (gamma(c)) chain heterodimer of the IL-2 receptor through trans-presentation by cells expres

270 eceptor binding surfaces and the core of the IL-2 structure, our results offer a direct blueprint for

271 nts with TB have DNA hypermethylation of the IL-2/STAT5, TNF/NF-kappaB, and IFN-gamma signaling pathw

272 tokine interleukin-2 (IL-2) that bind to the IL-2 receptor betagamma(c) heterodimer (IL-2Rbetagamma(c

273 ation of the IL-2 pathway with a bias to the IL-2 receptor CD122 (IL-2Rbeta).

274 rplasia, suggesting a mechanism by which the IL-2/IL-2R system may impact this widespread vascular pa

275 This IL-2-dependent scaling of thymic T reg cell generation b

276 nctional markers simultaneously (CD154, TNF, IL-2, and IFN-gamma).

277 ction, Treg cells retain selective access to IL-2 that supports their anti-inflammatory functions in

278 eo-2/15 has superior therapeutic activity to IL-2 in mouse models of melanoma and colon cancer, with

279 regulating NK cells that is not afforded to IL-2 and is distinct from activation by soluble IL-15.

280 lls in murine spleens and tumors compared to IL-2, and enhances the polyfunctionality of T and NK cel

281 cancer and solid tumor cells as compared to IL-2-activated non-expanded NK cells.

282 lting in T cells that were hyporesponsive to IL-2.

283 n of IL-2Rbeta and were unable to respond to IL-2 stimulation.

284 ment with anti-PD-L1, but instead respond to IL-2.

285 p-1 prevented GzmB expression in response to IL-2, suggesting two independent programs required for p

286 otoxin (interleukin-2 with diphtheria toxin [IL-2-DT]), or two combinations of both.

287 Unstimulated IL-2 and IFN-gamma were ranked at or near the top for al

288 vely express HPGDS and upregulate COX-2 upon IL-2, IL-25, and IL-33 plus thymic stromal lymphopoietin

289 cally with the cytokine IL-4 by upregulating IL-2-STAT5 signaling and reducing inhibitory histone tri

290 joints as compared to control joints, while IL-2, IL-6, IL-8, and TNF-alpha concentrations did not d

291 e of anti-tumor T cells compared to ACT with IL-2, resulting in superior antitumor activity in a B16-

292 exposure was also inversely correlated with IL-2, GM-CSF, and eotaxin production to Toll-like recept

293 +) transgenic OT-1 cells differentiated with IL-2 and IL-4 (T(C)2 cells) were exposed to normoxia (21

294 ntiation by biasing T cell interactions with IL-2-consuming DCs, but instead, directly regulates gene

295 llenged mice, which had been pretreated with IL-2/alphaIL-2 complexes in the presence or absence of a

296 However, the combination of rapamycin with IL-2 for 3 weeks significantly prolonged human islet all

297 promotes ASC development by synergizing with IL-2 and TLR7/8 ligands to induce genome-wide epigenetic

298 tably, application of allergen together with IL-2/alphaIL-2 complexes induced expression of Treg mark

299 WT) ATL cells but not cells transfected with IL-2, suggesting that in IL-2-producing cells signaling

300 [1-83], p=0.04), and with reduced CSF IFN-y, IL-2, and TNF-alpha concentrations (11.4 vs. 56.0pg/mL p